There is a continuing need for better and greater varieties of local anesthetics. However, the search for new anesthetics has been hampered by the lack of a definitive understanding of the molecular mechanism of local anesthetic action. Although there is considerable information on the interaction between membrane lipids and local anesthetics, there is little experimental data on such interaction with membrane proteins. In order to formulate a mechanism of local anesthetic action, there is a need for more information on these membrane protein - local anesthetic interactions. The first objective of this research is to establish definitely whether or not local anesthetics interact with membrane proteins. Our preliminary results, as well as the existing literature, suggest they do. Provided the interaction exists, we will detrmine the nature of this membrane protein - local anesthetic interaction. The significance of protein net charge and the involvement of protein conformation change in local anesthetic action will be studied. The characteristics of local anesthetic binding to the biological membranes (such as orientation, location, and number) and its importance will also be examined. Fluorescent probes and spin-labeled local anesthetics will be used to study the interaction between local anesthetics and membrane proteins.